Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis

Drewry, Anne M.; Ablordeppey, Enyo; Murray, Ellen; Stoll, C; Izadi, Sonya; Dalton, Catherine M.; Hardi, Angela; Fowler, Susan A.; Fuller, Brian M.; Colditz, Graham A.

doi:10.1097/ccm.0000000000002285

Cited by 66 publications

(26 citation statements)

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“…27,28 Retrospective and observational studies have even suggested benefit to elevated temperatures which in turn enhance the immune system and inhibit pathogen infectivity. [29][30][31][32][33][34][35] Our practice pattern was to utilize external or systemic temperature management devices to combat severe hyperthermia with the goal of inducing normothermia, not hypothermia. This practice pattern was left to the discretion of the attending intensivist as temperature management devices were limited and continually triaged among patients with the most severe hyperthermia.…”

Section: Discussionmentioning

confidence: 99%

Fever in the ICU: A Predictor of Mortality in Mechanically Ventilated COVID-19 Patients

Choron

Butts

Bargoud

et al. 2020

J Intensive Care Med

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Purpose: While fever may be a presenting symptom of COVID-19, fever at hospital admission has not been identified as a predictor of mortality. However, hyperthermia during critical illness among ventilated COVID-19 patients in the ICU has not yet been studied. We sought to determine mortality predictors among ventilated COVID-19 ICU patients and we hypothesized that fever in the ICU is predictive of mortality. Materials and Methods: We conducted a retrospective cohort study of 103 ventilated COVID-19 patients admitted to the ICU between March 14 and May 27, 2020. Final follow-up was June 5, 2020. Patients discharged from the ICU or who died were included. Patients still admitted to the ICU at final follow-up were excluded. Results: 103 patients were included, 40 survived and 63(61.1%) died. Deceased patients were older {66 years[IQR18] vs 62.5[IQR10], ( p = 0.0237)}, more often male {48(68%) vs 22(55%), ( p = 0.0247)}, had lower initial oxygen saturation {86.0%[IQR18] vs 91.5%[IQR11.5], ( p = 0.0060)}, and had lower pH nadir than survivors {7.10[IQR0.2] vs 7.30[IQR0.2] ( p < 0.0001)}. Patients had higher peak temperatures during ICU stay as compared to hospital presentation {103.3°F[IQR1.7] vs 100.0°F[IQR3.5], ( p < 0.0001)}. Deceased patients had higher peak ICU temperatures than survivors {103.6°F[IQR2.0] vs 102.9°F[IQR1.4], ( p = 0.0008)}. Increasing peak temperatures were linearly associated with mortality. Febrile patients who underwent targeted temperature management to achieve normothermia did not have different outcomes than those not actively cooled. Multivariable analysis revealed 60% and 75% higher risk of mortality with peak temperature greater than 103°F and 104°F respectively; it also confirmed hyperthermia, age, male sex, and acidosis to be predictors of mortality. Conclusions: This is one of the first studies to identify ICU hyperthermia as predictive of mortality in ventilated COVID-19 patients. Additional predictors included male sex, age, and acidosis. With COVID-19 cases increasing, identification of ICU mortality predictors is crucial to improve risk stratification, resource management, and patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Fever in the ICU: A Predictor of Mortality in Mechanically Ventilated COVID-19 Patients

Choron

Butts

Bargoud

et al. 2020

J Intensive Care Med

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“…Rather, the panel had to consider indirect data extrapolated from studies in adults. One systematic review of adult patients studied the use of antipyretics and physical cooling methods included eight RCTs (1507 patients) and eight observational studies (17,432 patients) [361]. This study had 28-day mortality as the primary outcome, with additional outcomes of early mortality (i.e., death on or prior to day 14), frequency of acquisition of hospital-acquired infection, frequency of shock reversal, and mean changes in body temperature, heart rate, and minute ventilation.…”

Section: We Suggest Either Antipyretic Therapy or A Permissive Approamentioning

confidence: 99%

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

et al. 2020

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Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those The Society of Critical Care Medicine guidelines are intended for general information only, are not medical advice, and do not replace professional advice, which should be sought for any medical condition. The full disclaimer for guidelines can be accessed at https ://www.sccm.org/Resea rch/Guide lines /Guide lines . panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods:The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, "in our practice" statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results:The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 49 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, "in our practice" statements were provided. In addition, 52 research priorities were identified. Conclusions:A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research. S14 the group heads, panel members, and methodologists. Searches utilized ...

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“…If the temperature increases without a greater proportional rise in heat production, overall entropy production is reduced; thus, suppressing fever where entropy production is decreased may be beneficial. Currently, antipyresis used indiscriminately in critically ill patients with sepsis has a minimal effect [ 92 ]. Analogously, therapeutic hypothermia, which involves cooling patients, may be useful in helping to maintain or enhance entropy production locally or systemically, provided the cooling does not reduce metabolism and heat production more than the drop in temperature.…”

Section: Evaluation and Implicationsmentioning

confidence: 99%

Optimizing Our Patients’ Entropy Production as Therapy? Hypotheses Originating from the Physics of Physiology

Seely

2020

Entropy

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Understanding how nature drives entropy production offers novel insights regarding patient care. Whilst energy is always preserved and energy gradients irreversibly dissipate (thus producing entropy), increasing evidence suggests that they do so in the most optimal means possible. For living complex non-equilibrium systems to create a healthy internal emergent order, they must continuously produce entropy over time. The Maximum Entropy Production Principle (MEPP) highlights nature’s drive for non-equilibrium systems to augment their entropy production if possible. This physical drive is hypothesized to be responsible for the spontaneous formation of fractal structures in space (e.g., multi-scale self-similar tree-like vascular structures that optimize delivery to and clearance from an organ system) and time (e.g., complex heart and respiratory rate variability); both are ubiquitous and essential for physiology and health. Second, human entropy production, measured by heat production divided by temperature, is hypothesized to relate to both metabolism and consciousness, dissipating oxidative energy gradients and reducing information into meaning and memory, respectively. Third, both MEPP and natural selection are hypothesized to drive enhanced functioning and adaptability, selecting states with robust basilar entropy production, as well as the capacity to enhance entropy production in response to exercise, heat stress, and illness. Finally, a targeted focus on optimizing our patients’ entropy production has the potential to improve health and clinical outcomes. With the implications of developing a novel understanding of health, illness, and treatment strategies, further exploration of this uncharted ground will offer value.

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Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis

Abstract: Supplemental Digital Content is available in the text.

Cited by 66 publications

References 50 publications

Fever in the ICU: A Predictor of Mortality in Mechanically Ventilated COVID-19 Patients

Fever in the ICU: A Predictor of Mortality in Mechanically Ventilated COVID-19 Patients

Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children

Optimizing Our Patients’ Entropy Production as Therapy? Hypotheses Originating from the Physics of Physiology

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